Figure 1. Schematic regulation of angiogenesis under conditions of hypoxia and nutrient starvation. Tumor tissue induces both hypoxic and nutrient-starved regions. The perivascular region (vascular rich) is rich in both oxygen and nutrients. The surrounding region has fewer nutrients, which induces JHDM1D expression (+++) and suppresses angiogenesis (+/−). Regions distal to the vascular-rich area become hypoxic and starved of nutrients, which stimulates induction of angiogenic factors (+++) resulting in an increase in expression of JMJD1A and angiogenesis (+++). Hypoxia and nutrient starvation suppresses cell cycle progression, but enriches non-proliferating cancer stem cells, contributing to tumor aggressiveness.